Autism is currently defined as a single disorder characterized by impairments in communication and social interaction and the presence of restricted or repetitive behaviors. The current diagnostic definition is based on behavioral characteristics, but there is mounting evidence that autism may be a collection of overlapping neurodevelopmental disorders, resulting from neuroanatomical, neurophysiological, neuroimmunologic and/or genetic abnormalities. The wide range of possible etiologies and the wide heterogeneity of symptom expression among individuals with autism has caused some to speculate that there may be several ?autism(s)?, i.e., subtypes of the disorder that have distinct causes and treatment considerations. The PDN research program aims to characterize the behavioral and biological manifestations of these subtypes of autism, in an effort to identify their etiologies and develop more effective treatments. A longitudinal phenomenological study of subtypes of autism has launched and is recruiting young children with non-regressive autism and regressive autism, as well as comparison groups of children with Rett Syndrome, developmental delay, and typical development. The study includes investigation of immunologic hypotheses, as well as exploration of EEG activity, MRI findings, sleep disturbance, environmental exposures, early medical history, genetics, genomics, and dysmorphology. Also underway is an open trial of minocycline, a tetracycline-related antibiotic with immunomodulatory properties. Children with regressive autism will be treated for six months with minocycline to determine whether or not they have behavioral improvements and changes in concentrations of CSF and/or serum cytokines. If benefits are seen in the open-label trial, a placebo-controlled investigation will be undertaken. The utility of chelation, a method for extraction of heavy metals, is also being investigated through a randomized controlled trial of meso-2,3-dimercaptosuccinic acid (DMSA; succimer), in children with autism spectrum disorders. This trial will test the efficacy of chelation, which is widely used in the community but has not been subjected to placebo-controlled trials. Benefits will be defined by behavioral improvements in this three-months long trial, and rates of heavy metal excretion will be tested to determine whether or not some children have abnormalities in their ability to process mercury and other heavy metals.